On August 30^th, the world- renowned academic journal Cell Research (cell research, IF=14.812) published online the research paper co-authored by  Song Baoliang’s research group from School of Life Sciences of Wuhan University and Yan Yan’s research group of Zhongshan Hospital Affiliated to Shanghai Fudan University (Cell Res.2016 Aug 30 doi: 10.1038/cr.2016.101.). This paper titled Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac syndrome presents the research that successfully cures cardiac syndrome PRKAG2 in a mouse model with CRISPR/Cas9 delivered by adeno-associated virus 9 (AAV9).

PRKAG2 cardiac syndrome is an autosomal dominant genetic disease, caused by PRKAG2 gene defects of AMPK protein kinase g2 subunit. Its main pathological features are myocardial glycogen storage, myocardial hypertrophy, ventricular preexcitation and progressive conduction system disease. PRKAG2 cardiac syndrome is likely to provoke sudden cardiac death. The continuous development of cardiac muscle cells will eventually lead to heart failure, and heart transplantation is then required.

The researchers detect H530R mutation of AMPKg2 in ailing families, and construct models of transgenic mice and gene knock-in mice to express the mutant gene. The main pathological features of the patients are successfully reproduced in the two mice models, and it is the first time that this mutation leading to the occurrence of PRKAG2 cardiac syndrome has been confirmed. 

The researchers load the gene editing tool CRISPR/Cas9 into the safe and efficient AAV9 and delivered it to the specific expression in the mouse heart to achieve type-specific editing mutant alleles. It can significantly reverse the main indicators of heart disease. For the first time, it is confirmed that CRISPR/Cas9 gene therapy strategy can be applied to dominant genetic heart disease in humans.

Dr. Xie Chang, Dr. Zhang Yaping and Dr. Song Lu are the co-first author of the paper, while Professor Song Baoliang and Professor Yan Yan are corresponding authors. This research gains support from the National Ministry of Science and Technology, the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. 

Pictures:

A. schematic diagram of the role of CRISPR/Cas9.The sgRNA created and the mutant PRKAG2 gene match perfectly, and can type-specifically act on mutant alleles without cutting the wild type allele.

 B. H530R mutant mouse’s heart returns to normal cardiac size after injecting AAV9-CRISPR.

( Rewritten by Wang Hanxu, edited by Shen Yuxi & Hu Sijia)